Effect of Gamma Tocopherol Enriched Supplementation on Response to Inhaled LPS

Inclusion Criteria

• Age 18-50 of both genders
• Negative pregnancy test for females who are not s/p hysterectomy with oophorectomy
• History of episodic wheezing, chest tightness, or shortness of breath consistent with asthma, or physician diagnosed asthma.
• Positive methacholine test. A positive test is defined as a provocative concentration of methacholine of 10 mg/ml or less producing a 20% fall in Forced Expiratory Volume in 1 second (FEV1) (PC20 methacholine) by the method used in a separate screening protocol.
• FEV1 of at least 80% of predicted and FEV1/FVC ratio of at least .70 (without use of bronchodilating medications for 12 hours or long acting beta agonists for 24 hours), consistent with lung function of persons with no more than mild episodic or mild persistent asthma.
• Allergic sensitization to at least one of the following allergen preparations: (House Dust Mite f, House dust mite p, Cockroach, Tree mix, Grass Mix, Weed Mix, Mold Mix 1, Mold Mix 2, Rat, Mouse, Guinea Pig, Rabbit, Cat or Dog) confirmed by positive immediate skin test response.
• Symptom Score (this will be submitted as an attachment) no greater than 16 (out of a possible 24) for total symptom score with a value no greater than 3 for any one score. No more than one score may be greater or equal than 3.
• subjects must be willing to avoid caffeine for 12 hours prior to all visits.

Exclusion Criteria

• Any chronic medical condition considered by the PI as a contraindication to the exposure study including significant cardiovascular disease, diabetes, chronic renal disease, chronic thyroid disease, history of chronic infections/immunodeficiency, history of tuberculosis
• Physician directed emergency treatment for an asthma exacerbation within the preceding 12 months
• Moderate or Severe asthma
• Exacerbation of asthma more than 2x/week which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma.
• Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest tightness) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current National Heart, Lung and Blood Institute (NHLBI) guidelines for diagnosis and management of asthma. (Not to include prophylactic use of albuterol prior to exercise).
• Viral upper respiratory tract infection within 2 weeks of challenge.
• Any acute infection requiring antibiotics within 2 weeks of exposure or fever of unknown origin within 2 weeks of challenge.
• Severe asthma
• Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
• Medications which may impact the results of the Clinical Center Reference Endotoxin (CCRE) exposure, interfere with any other medications potentially used in the study (to include steroids, beta antagonists, non-steroidal anti-inflammatory agents)
• Any history of smoking in the year prior to study enrollment; lifetime smoking history > 10 pack years
• Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a clearly recognized viral induced asthma exacerbation) which would be characteristic of a person of moderate or severe persistent asthma as outlined in the current NHLBI guidelines for diagnosis and management of asthma
• Allergy/sensitivity to study drugs, including E coli, or their formulations.
• Known hypersensitivity to methacholine or to other parasympathomimetic agents
• History of intubation for asthma
• Unwillingness to use reliable contraception if sexually active (Intrauterine device, birth control pills/patch, condoms).
• Abnormal Prothrombin Time (PT) or Partial Thromboplastin Time (PTT) values at screening or during the treatment period. Normal values will be those published by the clinical lab (Labcorp, INC).
• Any bleeding